Hemodynamic Management After Spinal Cord Injury

By Rachel C. Stratman, PharmD; Ann M. Wiesner, PharmD; Kelly M. Smith, PharmD, BCPS, FASHP; Aaron M. Cook, PharmD
ORTHOPEDICS 2008; 31:252
March 2008

Practitioners can play an active role in the implementation of hemodynamic support as part of aggressive management of spinal cord injuries to prevent systemic hypotension, limit posttraumatic ischemia, and optimize neurologic recovery.

Optimal neurologic recovery in patients with spinal cord injuries is best achieved through the provision of prompt, comprehensive patient care. Evidence-based practices in patients with spinal cord injury are sparse, leaving practitioners in a state of clinical equipoise on many issues in spinal cord injury care. The manipulation of systemic blood pressure by volume expansion agents and vasopressors after acute spinal cord injury is an example in which clinical data are limited. Data from experimental models and extrapolation from other neurotrauma models, (eg, traumatic brain injury) suggest that preventing neuronal (spinal cord) hypoperfusion is among the most important supportive measures a practitioner can control. This article reviews the pathophysiology of neuronal injury along with the literature supporting hemodynamic management and discusses volume and blood pressure management strategies required to maintain spinal cord perfusion and prevent the progression of neuronal damage, as recommended by the spinal cord injury guidelines.

Neuronal Injury
Acute spinal cord injury involves both primary and secondary mechanisms of injury. Primary injury refers to the damage incurred during the original trauma. The severity of primary injury is the strongest prognostic indicator of morbidity and mortality.1,2 In many instances, primary injury is preventable. However, once the primary spinal cord injury has occurred, options are limited. Supportive care and expeditious surgical decompression of the spinal cord are the principal interventions that may attenuate the immediate effects of the injury.

Spinal cord damage due to primary injury is immediate and typically due to physical destruction and necrosis of the neuronal cells. In contrast, secondary injury occurs in the hours to days following the original insult and is typified by an insidious cascade of events involving spinal cord ischemia, release of numerous deleterious neurotransmitters, cytotoxic edema, lipid peroxidation, and apoptosis.

Secondary injury compromises the restorative capabilities of the spinal cord and contributes extensively to morbidity after spinal cord injury.1 Key components of secondary injury that lead to neurologic demise are loss of microcirculation, loss of autoregulation, and development of ischemia.1,3 Unlike primary injury, secondary injury appears to be modifiable. As a result, it often is the target of pharmacologic agents. Experimental therapies (eg, methylprednisolone, naloxone, and tirilazad) have been used early in spinal cord injury to mitigate secondary injury, with only methylprednisolone exhibiting clinical benefit. Favorable outcomes have also been associated with aggressive hemodynamic management aimed at restoring spinal cord perfusion and preventing irreversible neuronal damage caused by ischemia.

Under normal physiologic conditions, spinal cord perfusion is maintained through autoregulatory mechanisms that appear similar to those that regulate cerebral perfusion.3-7 Aggressive volume and blood pressure management to avoid hypotension in patients with cerebral ischemia increases cerebral perfusion pressure and improves neurologic outcomes compared to those without aggressive management.8-13

Experimental models demonstrate that in the absence of autoregulation, spinal cord perfusion is proportional to systemic blood pressure.14 One frequently cited study described the neurological outcomes in patients with spinal cord injuries who were treated with high-dose methylprednisolone and early, aggressive volume resuscitation.2 Blood pressures were titrated to achieve a mean arterial pressure of 85 mmHg for the first 7 days after the spinal cord injury. This study compared a prospective cohort with historical controls managed without aggressive hemodynamic management.

The selection of the mean arterial pressure target of 85 mmHg in this and other studies evaluating aggressive treatment of spinal cord injury was arbitrary; however, claims of neurologic improvement associated with aggressive management after spinal cord injury have led to the acceptance of maintaining mean arterial pressure at high to normal levels of 85 to 90 mmHg.15-20

Evidence supporting the optimal duration of aggressive management is also lacking, further emphasizing the need for a randomized controlled trial to determine the mean arterial pressure that best promotes neuronal recovery (or prevents further injury) and the duration that it should be maintained.

Hemodynamic instability in spinal cord injury is associated with multiple causes, including hemorrhage, tension pneumothorax, myocardial injury, pericardial tamponade, and sepsis.21 Most unique to patients with spinal cord injury is neurogenic shock, which is manifested by a nearly total loss of sympathetic activation and control of cardiac function by the cranial nerves. As a consequence, patients often exhibit signs of systemic hypotension and bradycardia. Invasive hemodynamic monitoring through arterial and Swan-Ganz pulmonary artery catheters allows for the continuous measurement of peripheral resistance and cardiac output. This aids in the guidance of fluid resuscitation and vasopressor therapy in an attempt to maintain adequate spinal cord perfusion and prevent secondary injury.

Fluid Resuscitation
Providing adequate fluid resuscitation is paramount in patients presenting with acute spinal cord injury. Therapeutic options for volume expansion in patients with spinal cord injury include crystalloids, colloids, blood products, or a combination of these options. In the Saline versus Albumin Fluid Evaluation study, 6997 intensive care unit patients were randomized to receive either 4% albumin or 0.9% normal saline for fluid resuscitation.22 The results of this trial indicated no difference in the 28-day rate of death from any cause; however, a subgroup analysis of trauma patients revealed an increased risk of death among those who received albumin. Currently, the optimal type of fluid in patients with spinal cord injury is unknown. However, due to the data indicating a possible increased mortality in trauma patients randomized to albumin resuscitation, iso-osmotic crystalloids such as 0.9% sodium chloride are typically preferred. Fluids such as dextrose 5% in water and 0.45% sodium chloride should be avoided due to the risk of exacerbating intracellular edema.23 Blood products may also be useful to maintain oxygen delivery and prevent further ischemic injury in patients with extensive injuries and associated blood loss. Patients with spinal cord injury are also at risk of developing pulmonary edema due to fluid shifts after injury; therefore, judicious fluid resuscitation (guided by invasive monitoring when necessary) is recommended.

Vasoactive Agents
The cardiovascular response in patients presenting with acute spinal cord injury often is altered beyond that of volume depletion. Hypotension that fails to resolve with adequate fluid resuscitation often is related to the severity and location of spinal injury. Loss of autoregulation and reduced sympathetic activity leads to hypotension, cardiac bradyarrhythmias, decreased peripheral vascular resistance, and reduced cardiac output.2,5,18-20,24 More profound effects are seen with injuries in the cervical or upper thoracic regions and with complete spinal injuries.24,25 Vasopressors and inotropes may be indicated in the presence of decreased systemic vascular resistance, despite adequate volume expansion. In patients with acute spinal cord injury, the vasopressor of choice depends on the patient’s hemodynamic profile, but often is one that has both a- and b-adrenergic activity.

Numerous adrenergic agonists are available to augment blood pressure in patients with spinal cord injury (Table). Dopamine is a catecholamine-like agent that is a chemical precursor of norepinephrine, which produces a dose-dependent hemodynamic effect. Although multiple endocrine and immune complications are also associated with dopamine use, this agent may be particularly useful in patients with spinal cord injury who also have hypotension and bradycardia, or in those who need increased cardiac output.26

Norepinephrine is a direct-acting catecholamine with some inotropic activity. Like dopamine, norepinephrine may be especially useful in patients with neurogenic hypotension and bradycardia. Phenylephrine is a direct-acting vasopressor that solely acts on a1 receptors, resulting in systemic vasoconstriction. Without concomitant b-agonism, phenylephrine typically results in a reflexive bradycardia and should be used with caution if patients have a history of bradycardia after spinal cord injury.

Several other commonly available vasoactive agents may have a limited role in patients with spinal cord injury. Epinephrine is a catecholamine that is primarily used to treat anaphylactic reactions an d cardiac arrest. This agent should be considered for patients with hypotension refractory to dopamine and norepinephrine. Vasopressin is a vasopressor that often is used to treat patients with diabetes insipidus or septic shock, in which it may decrease the requirement for high infusion rates of catecholamines. Aquaporin water channels, involved in the regulation of membrane permeability, can be activated by vasopressin. The precise role of aquaporin receptors and vasopressin in the pathogenesis of edema and secondary injury in spinal cord injury is ill-defined. In addition, the antidiuretic effects of vasopressin may lead to increased water retention and hyponatremia, which may exacerbate intracellular edema after spinal cord injury. Thus, the role for vasopressin in spinal cord injury is not well defined, and it should be used with extreme caution. Dobutamine is a synthetic catecholamine, often classified as an inodilator. In addition to the potent effects on the ?1 receptor that increases cardiac output, dobutamine causes mild vasodilation, decreasing afterload. Dobutamine is an option to increase systemic oxygen delivery in patients with spinal cord injury with decreased cardiac output or diminished ejection fraction.

Complications from these potent vasoactive agents are common without proper monitoring. High doses of vasopressors for prolonged periods of time should be avoided to prevent the detrimental effect of decreased organ perfusion due to potent vasoconstriction—particularly in the extremities, gastrointestinal tract, and kidneys. Intravascular volume overload and induction of supranormal blood pressure in patients with spinal cord injury can cause pulmonary and cerebral edema. Achievement of adequate hemodynamic support should include stabilization of vital signs and hemodynamic parameters, in addition to achieving and maintaining adequate urine output and oxygenation.

The optimal management of traumatic spinal cord injury has yet to be established. Current management strategies include early immobilization, rapid transport to an equipped institution, and administration of pharmacologic agents (eg, methylprednisolone) to prevent secondary injury. Practitioners can play an active role in the implementation of hemodynamic support as part of aggressive management of spinal cord injury to prevent systemic hypotension, limit posttraumatic ischemia, and optimize neurologic recovery. Restoration of the circulatory volume through the use of volume expansion products, such as crystalloids and colloids, is essential prior to the initiation of vasopressors. Hypotension that persists despite adequate fluid resuscitation may require vasopressors (eg, dopamine, norepinephrine, or phenylephrine) or the addition of an inodilator (eg, dobutamine). Further research is needed to better define the systemic blood pressure which optimizes spinal perfusion, duration of the loss of spinal autoregulation, and preferable vasopressor options after spinal cord injury.

The Bottom Line
Avoidance of hypotension after spinal cord injury may ensure adequate spinal cord perfusion and limit the extent of posttraumatic ischemia.
Maintaining a mean arterial pressure of 85 to 90 mmHg for the first 7 days after spinal cord injury has been suggested to improve neurologic outcomes.
Restoration of circulatory volume is essential prior to the use of vasopressors.
The selection of vasopressors should be guided by the patient’s hemodynamic profile.

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Authors
Rachel C. Stratman, PharmD; Ann M. Wiesner, PharmD; Kelly M. Smith, PharmD, BCPS, FASHP; Aaron M. Cook, PharmD

Drs Stratman, Wiesner, and Cook are from University of Kentucky HealthCare, and Dr Smith is from University of Kentucky College of Pharmacy, Lexington, Kentucky.

Drs Stratman, Wiesner, Smith, and Cook have no relevant financial relationships to disclose.

Correspondence should be addressed to: Aaron M. Cook, PharmD, 800 Rose St, H-110, Lexington, KY 40536-0293.

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